Nuclear Export

Abstract

One of the distinguishing features of eukaryotic cells is the compartmentalization of genetic information within a membrane-enclosed nucleus. The double membrane of the nuclear envelope separates the nucleus and the cytoplasm, and all macromolecu-lar exchange across the nuclear envelope takes place through large protein channels termed the nuclear pore complexes (NPCs). The molecules that are exchanged between these two com-partments range in size from ions and other small molecules to large complexes such as the 5OS ribosome and other large ribonucleoprotein complexes. In contrast to ions and small proteins that diffuse across the NPC, macromolecular movement is an active process. Active nucleocy-toplasmic transport allows for the proper compartmentalization of nuclear proteins involved in transcription, replication of DNA, and remodeling of chromatin. Transport also is necessary for mRNAs, tRNAs, and rRNAs that are transcribed in the nucleus but ultimately function in the cytoplasm. This growing awareness of the role of nuclear transport in regulating gene ex-pression has paralleled a remarkable increase in our knowledge of the nuclear transport process itself. Far from acting as static “localization signals” the sequences specifying nuclear location act in combination with other signals to alter the steady-state distribution of nuclear proteins. Thus, the concept of nuclear proteins shuttling between nucleus and cytoplasm has emerged as a dominant principle in understanding nuclear import and export. It is impossible to look at nuclear export in isolation without considering nuclear import rates. This has proven to be a barrier in understanding nuclear export as a process with distinct features and requirements. The number of import and export carriers identified has grown to include factors specific for classes of nuclear components and more general factors. In addition, it is clear that movement through the nuclear pore complex is dictated by properties of both the pore and the carrier molecules themselves. These properties are reflected in binding interactions that may facilitate movement across the nuclear pore and perhaps provide for directionality of transport. In this brief chapter, we will give a brief overview of the nuclear pore complex, methods for examining nuclear export and shutding, the nature of the transport machinery and nuclear export carri-ers. We will then attempt to combine these into a coherent model for understanding nuclear import and export. We do not claim that this is a comprehensive overview. A number of excel-lent reviews of this type have recendy appeared (see for example refs. 1,2). What we hope to do is point out some novel aspects of nuclear export and emphasize some recent findings which suggest that factors other than traditional transport carriers may be involved and regulate the process of nuclear shuttling.